The cyclic GMP-dependent protein kinase II gene associates with gout disease identified by genome-wide analysis and case-control study

Shun-Jen Chang ^1*, Ming-Hsien Tsai ¹, Ying-Chin Ko ¹, Pei-Chien Tsai ¹, Chung-Jen Chen ² and Han-Ming Lai ²

¹ Kaohsiung Medical University, Taiwan
² Chang Gung Memori Hospital- Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan

^* To whom correspondence should be addressed. E-mail: changsj{at}kmu.edu.tw.

Accepted 26 July 2008

Abstract

Objectives: To identify the position of a gout susceptibility gene.

Methods: We performed a genome-wide scan method using 382 random polymorphic microsatellite markers spread across 22 autosomes in a Taiwanese gout family to screen the gout susceptibility genetic marker. We confirmed its association with gout disease by 33 single nucleotide polymorphisms (SNP) in 148 matched case-control subjects. The gout family was composed of eight gouty patients and ten gout-free subjects and the case-control subjects were 74 male gout patients and 74 healthy controls matched by age.

Results: Analysis of the genome-wide scan result by a non- parametric linkage method found that chromosome 4q21 contains a locus significantly linked with gout disease (D4S3243 at 81,289,553 bp; p = 0.004; LOD score = 5.13). In SNP genotyping analysis at the neighborhood regions of marker D4S3243 for the case-control subjects, the polymorphisms rs7688672 and rs6837293, located on the cGMP-dependent protein kinase II (cGK II) gene, were found to relate significantly to gout disease in a recessive model after adjustment of hyperuricemia (OR=2.89, 95% CI=1.19-7.02 and OR=2.72, 95% CI=1.13-6.54 respectively).

Conclusions: This study suggests the cGK II gene on chromosome 4q21 was most likely to harbor gout disease independent of hyperuricemia and inherited recessively.